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Does Metformin Blunt Diabetes Link to Brain Aging?

0 2 years ago

Why This Matters

  • Although preliminary evidence links type 2 diabetes to neurologic and cognitive decline, patients don’t typically undergo comprehensive neurocognitive evaluation as part of clinical care.
  • It is currently unknown whether neurocognitive effects represent a type 2 diabetes-specific neurodegenerative pathway or exacerbation of typical brain aging.
  • Few studies have addressed the impact of type 2 diabetes chronicity or treatment on neurocognitive decline.

  • Neurocognitive effects independently associated with type 2 diabetes and age were examined in 20,314 individuals from the UK Biobank.
  • A separate meta-analysis evaluated 34 published cognitive studies (N = 22,231) and 60 neuroimaging studies, 30 of type 2 diabetes (N = 866) and 30 of aging (N = 1088).

Key Results

  • In the UK Biobank, cognitive deficits beyond age-related effects were seen among those with type 2 diabetes, particularly an additional 13.1% decreased performance in executive function (P = .001) and a 6.7% greater decline in processing speed (P = .0002).
  • The meta-analysis confirmed further declines with type 2 diabetes in executive function (P = .009), processing speed (P ≤ .001), and numeric memory (approximately 2-3 seconds, P = .05), as well as abstract reasoning (P ≤ .001), verbal memory (P = .001), delayed (approximately 20 minute) verbal memory (P = .005), verbal fluency (P ≤ .001), visuospatial reasoning (P ≤ .001), and working memory (P = .002).
  • Compared to age-matched controls, those with type 2 diabetes had further decreases in gray matter including cortical and subcortical regions.
  • Structural and functional changes associated with type 2 diabetes overlapped with those associated with age but appeared earlier.
  • Neurodegeneration severity correlated with diabetes duration.
  • No differences in cognition or brain atrophy between those with type 2 diabetes who were or were not taking metformin was seen, after matching for disease duration and body mass index.


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